Background Simplified approaches of acute malnutrition (AM) treatment have been conducted over the past 5 years intending to unify processes and increase coverage among children aged 6 to 59 months without medical complication. The Optimsing treatment for Acute Malnutrition (OptiMA) and the Combined Protocol for Acute Malnutrition Study (ComPAS) are mid-upper arm circumference (MUAC)-based approaches treating children with MUAC < 125 mm or oedema with one sole product—ready-to-use therapeutic food—at a gradually tapered doses. This trial aims to compare the OptiMA and ComPAS strategies to the standard nutritional protocol of Niger assessed by a favourable outcome in the treatment of uncomplicated AM at 6 months post-randomisation and in terms of recovery rate after treatment of uncomplicated SAM (WHZ < − 3 or MUAC < 115mm or oedema) and among the most vulnerable children (MUAC < 115mm or oedema). Methods A non-inferiority individually randomised controlled clinical trial was conducted at the primary health centres level and in the community in the Zinder region in Niger in March 2021. Participants are children aged 6–59 months attending outpatient health centres with MUAC < 125mm or oedema without medical complications. All participants are followed for 6 months. Simplified strategies propose a gradual reduction of RUTF according to MUAC and weight in OptiMA and MUAC only in ComPAS. Favourable outcome is compositely defined at 6 months post-inclusion as being alive, not acutely malnourished by the definition applied at inclusion and without any additional episode of AM throughout the 6-month observation period. Recovery is defined throughout the 6 months post-randomisation by a minimum of 4-week duration of treatment, an axillary temperature < 37.5°C, an absence of bipedal oedema and a MUAC ≥ 125 mm for two consecutive weeks. The sample size calculation required 567 children per arm for the main objective, 295 and 384 children per arm for the secondary objectives among SAM and MUAC < 115 mm children, respectively. Per-protocol and intention-to-treat analyses will be conducted for each outcome. Discussion This trial is intending to generate much-needed evidence on various simplified and optimised AM treatment approaches and to participate in reaching a consensus on such nutrition protocols. Trial registration ClinicalTrials.govNCT04698070. Registered on January 6, 2021